on April 24, 2008
Published online before print April 24, 2008, doi: 10.1161/ATVBAHA.108.162347
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Submitted on January 7, 2008
Accepted on March 26, 2008
Thrombocytopenia and Platelet Abnormalities in High-Density Lipoprotein Receptor–Deficient Mice
Vandana S. Dole ;
From the Department of Biology (V.S.D., E.V., A.Y., M.K.), Massachusetts Institute of Technology, Cambridge; and Immune Disease Institute and Department of Pathology (J.M., W.B., M.B., D.D.W.), Harvard Medical School, Boston, Mass.
* To whom correspondence should be addressed. E-mail: Krieger{at}MIT.edu.
Objective—High-density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), mediated cellular uptake of lipoprotein cholesterol controls HDL structure and plasma HDL and biliary cholesterol levels. In SR-BI knockout (KO) mice, an unusually high plasma unesterified-to-total cholesterol ratio (UC:TC) and abnormally large HDL particles apparently contribute to pathology, including female infertility, susceptibility to atherosclerosis and coronary heart disease, and anemia. Here we examined the influence of SR-BI deficiency on platelets.
Methods and Results—The high plasma UC:TC ratio in SR-BI KO mice was correlated with platelet abnormalities, including high cholesterol content, abnormal morphologies, high clearance rates, and thrombocytopenia. One day after platelets from wild-type mice were infused into SR-BI KO mice, they exhibited abnormally high cholesterol content and clearance rates similar to those of endogenous platelets. Platelets from SR-BI KO mice exhibited in vitro a blunted aggregation response to the agonist ADP but a normal response to PAR4.
Conclusions—In SR-BI KO mice abnormal circulating lipoproteins, particularly their high UC:TC ratio—rather than the absence of SR-BI in platelets themselves—induce defects in platelet structure and clearance, together with a mild defect in function.
Key words: HDL receptor • SR-BI • platelet • thrombocytopenia • clearance